Age-related differences in metabolism and cerebral blood flow (rCBF), as measured by positron emission tomography (PET), were enhanced in frontal cortex when young and old subjects received sensory activation. Dorsal vs. ventral patterns of rCBF activation during face and location matching were similar in young and old subjects, but young subjects had more activation of occipital cortex and older subjects had more frontal activation. Activation of rCBF in occipitotemporal cortex was equivalent during face perception in patients with dementia of the Alzheimer type (DAT) and controls; patients also had frontal activation. The activation results are consistent with the hypothesis of reversible synaptic dysfunction in early Alzheimer's disease (AD). A patient with isolated memory impairment and family history for autosomal dominant AD was studied with PET twice and found to have normal glucose metabolism with routine analysis but both scans were abnormal using a discriminant function analysis. A patient with autopsy proven Parkinson's disease had a metabolic pattern indistinguishable from that seen in DAT. Regional densities of neurofibrillary tangles, but not of senile plaques in postmortem brain, were correlated with metabolic reductions in 5 AD patients who were scanned prior to death. A two-stage hypothesis of dementia in Down syndrome was suggested by longitudinal patterns of neuropsychological decline and measures of brain atrophy. Subjects with Turner syndrome (45,X), including mosaics, had reduced volume of the hippocampus, lower parietal metabolism and impairment of visuospatial abilities.